The atomic resolution structure of the P4-P6 domain of the Tetrahymena ribozyme that was solved by Doudna and co-workers provides an intimate look at the molecular contacts that stabilize the tertiary Hstructure of an RNA. Interestingly, our studies have shown that the Hformation of the tertiary contacts that form within the P5c subdomain Hoccur slightly faster than the concerted folding of the remainder of Hthe P4-P6 domain. The P5c subdomain contains crystallographically Hdiscernible Mg2+ ions and has been postulated to be the trigger for Hthe folding of the ribozyme. We are further exploring the folding Hmechanism of the Tetrahymena ribozyme by examining the folding of the Hisolated P4-P6 domain, which is seen to fold on the sub-second Htimescale in the presence of other ribozyme components. This work Halso provides the foundation for the analysis of mutations in P4-P6 Hthat enhance the rate of folding of the catalytic core, as described Hin the next subproject.